Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.

Novel, low-abundance microbial species can be easily overlooked in standard polymerase chain reaction (PCR)-based surveys. We used community genomic data obtained without PCR or cultivation to reconstruct DNA fragments bearing unusual 16S ribosomal RNA (rRNA) and protein-coding genes from organisms belonging to novel archaeal lineages. The organisms are minor components of all biofilms growing in pH 0.5 to 1.5 solutions within the Richmond Mine, California. Probes specific for 16S rRNA showed that the fraction less than 0.45 micrometers in diameter is dominated by these organisms. Transmission electron microscope images revealed that the cells are pleomorphic with unusual folded membrane protrusions and have apparent volumes of <0.006 cubic micrometer.

Management of airway infections caused byPseudomonas aeruginosa is a serious clinical challenge, but little is known about the microbial ecology of airway infections in intubated patients. We analyzed bacterial diversity in endotracheal aspirates obtained from intubated patients colonized by P. aeruginosa by using 16S rRNA clone libraries and microarrays (PhyloChip) to determine changes in bacterial community compositions during antibiotic treatment. Bacterial 16S rRNA genes were absent from aspirates obtained from patients briefly intubated for elective surgery but were detected by PCR in samples from all patients intubated for longer periods. Sequencing of 16S rRNA clone libraries demonstrated the presence of many orally, nasally, and gastrointestinally associated bacteria, including known pathogens, in the lungs of patients colonized with P. aeruginosa. PhyloChip analysis detected the same organisms and many additional bacterial groups present at low abundance that were not detected in clone libraries. For each patient, both culture-independent methods showed that bacterial diversity decreased following the administration of antibiotics, and communities became dominated by a pulmonary pathogen. P. aeruginosa became the dominant species in six of seven patients studied, despite treatment of five of these six with antibiotics to which it was sensitive in vitro. Our data demonstrate that the loss of bacterial diversity under antibiotic selection is highly associated with the development of pneumonia in ventilated patients colonized with P. aeruginosa. Interestingly, PhyloChip analysis demonstrated reciprocal changes in abundance between P. aeruginosa and the class Bacilli, suggesting that these groups may compete for a similar ecological niche and suggesting possible mechanisms through which the loss of microbial diversity may directly contribute to pathogen selection and persistence.

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Diabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be highly beneficial. Urine as a diagnostic medium allows for non-invasive detection of biomarkers, including some associated with type 2 diabetes and its complications. This review provides a synopsis of those urinary biomarkers that potentially may provide a basis for the development of improved diagnostic tests. Three main pathways for the sourcing of potential makers are identified: kidney damage, oxidative stress and low-grade inflammation including atherosclerosis/vascular damage. This review briefly presents each pathway and some of the most relevant urinary biomarkers that may be used to monitor the development or progression of diabetes and its complications. In particular, biomarkers of renal dysfunction such as transferrin, type IV collagen and N-acetyl-beta-D-glucosaminidase might prove to be more sensitive than urinary albumin, the current gold standard, in the detection of incipient nephropathy and risk assessment of cardiovascular disease. Inflammatory markers including orosomucoid, tumour necrosis factor-alpha, transforming growth factor-beta, vascular endothelial growth factor and monocyte chemoattractant protein-1, as well as oxidative stress markers such as 8-hydroxy-2'deoxyguanosine may also be useful biomarkers for diagnosis or monitoring of diabetic complications, particularly kidney disease. However, the sensitivity of these markers compared with albumin requires further investigation.

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Fluoroquinolone resistance and type III secretion system (TTSS) virulence are independently associated in Pseudomonas aeruginosa infections with poor patient outcomes. In the present study, the virulence of fluoroquinolone-susceptible and -resistant isolates of P. aeruginosa was compared, focusing on TTSS virulence. Clinical isolates (n = 45) exhibiting a broad range of susceptibilities to fluoroquinolones, with differing mechanisms of resistance and associated with varying disease sites, were selected for the study. PCR, Southern blot and western immunoblot analyses were performed to determine the presence of TTSS-encoding genes and secretion of gene products. The cytotoxicity of the clinical isolates towards human lung epithelial cells was also determined. Clinical isolates encoding only the exoS cytotoxin gene occurred more frequently than those encoding only exoU (62% vs. 27%; p 0.0007). Compared with exoS(+) isolates, exoU(+) isolates were more likely to be fluoroquinolone-resistant (92% vs. 61%, p 0.05) and to exhibit both a gyrA mutation and the efflux pump over-expressed (EPO) phenotype (91% vs. 59%; p 0.06). Almost all exoU(+) strains secreted ExoU and exhibited increased cytotoxicity compared with ExoS-secreting strains (7% vs. 92.5%, relative to a PA103 reference strain control). These data suggest that exoU(+) and fluoroquinolone resistance may be co-selected traits that result in highly virulent and resistant strains. Adverse outcomes associated with infections caused by fluoroquinolone-resistant strains may, in part, be attributable to this co-association, which warrants further clinical investigation.

Transforming growth factor-␤ (TGF-␤